Hormonal contraception alters vaginal microbiota and cytokines in South African adolescents in a randomized trial

Christina Balle, Iyaloo N. Konstantinus, Shameem Z. Jaumdally, Enock Havyarimana, Katie Lennard, Rachel Esra, Shaun L. Barnabas, Anna-Ursula Happel, Zoe Moodie, Katherine Gill, Tanya Pidwell, Ulas Karaoz, Eoin Brodie, Venessa Maseko, Hoyam Gamieldien, Steven E. Bosinger, Landon Myer, Linda-Gail Bekker, Jo-Ann S. Passmore and Heather B. Jaspan ()
Additional contact information
Christina Balle: University of Cape Town
Iyaloo N. Konstantinus: University of Cape Town
Shameem Z. Jaumdally: University of Cape Town
Enock Havyarimana: University of Cape Town
Katie Lennard: University of Cape Town
Rachel Esra: University of Cape Town
Shaun L. Barnabas: University of Cape Town
Anna-Ursula Happel: University of Cape Town
Zoe Moodie: Fred Hutchinson Cancer Research Center
Katherine Gill: University of Cape Town
Tanya Pidwell: University of Cape Town
Ulas Karaoz: Lawrence Berkeley National Laboratories
Eoin Brodie: Lawrence Berkeley National Laboratories
Venessa Maseko: National Institute for Communicable Diseases, Sandringham
Hoyam Gamieldien: University of Cape Town
Steven E. Bosinger: Emory University School of Medicine; Division of Microbiology and Immunology, Yerkes National Primate Research Center
Landon Myer: University of Cape Town
Linda-Gail Bekker: University of Cape Town
Jo-Ann S. Passmore: University of Cape Town
Heather B. Jaspan: University of Cape Town

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. However, hormonal contraceptive (HC) use may influence HIV risk through changes in genital tract microbiota and inflammatory cytokines. To investigate this, 130 HIV negative adolescent females aged 15–19 years were enrolled into a substudy of UChoose, an open-label randomized crossover study (NCT02404038), comparing acceptability and contraceptive product preference as a proxy for HIV prevention delivery methods. Participants were randomized to injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) or etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR) for 16 weeks, then crossed over to another HC for 16 weeks. Cervicovaginal samples were collected at baseline, crossover and exit for characterization of the microbiota and measurement of cytokine levels; primary endpoints were cervical T cell activation, vaginal microbial diversity and cytokine concentrations. Adolescents randomized to COCs had lower vaginal microbial diversity and relative abundance of HIV risk-associated taxa compared to Net-En or CCVR. Cervicovaginal inflammatory cytokine concentrations were significantly higher in adolescents randomized to CCVR compared to COC and Net-En. This suggests that COC use may induce an optimal vaginal ecosystem by decreasing bacterial diversity and inflammatory taxa, while CCVR use is associated with genital inflammation.

Date: 2020
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DOI: 10.1038/s41467-020-19382-9

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